The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation
Abstract
PURPOSE: Clonal hematopoiesis of indeterminate potential (CHIP) occurs in the blood of approximately 20% of older persons. CHIP is linked to an increased risk of hematologic malignancies and of all-cause mortality; thus, the eligibility of stem-cell donors with CHIP is questionable. We comprehensively investigated how donor CHIP affects outcome of allogeneic hematopoietic stem-cell transplantation (HSCT). METHODS: We collected blood samples from 500 healthy, related HSCT donors (age ≥ 55 years) at the time of stem-cell donation for targeted sequencing with a 66-gene panel. The effect of donor CHIP was assessed on recipient outcomes, including graft-versus-host disease (GVHD), cumulative incidence of relapse/progression (CIR/P), and overall survival (OS). RESULTS: A total of 92 clonal mutations with a median variant allele frequency of 5.9% were identified in 80 (16.0%) of 500 donors. CHIP prevalence was higher in donors related to patients with myeloid compared with lymphoid malignancies (19.2% v 6.3%; P ≤ .001). In recipients allografted with donor CHIP, we found a high cumulative incidence of chronic GVHD (cGVHD; hazard ratio [HR], 1.73; 95% CI, 1.21 to 2.49; P = .003) and lower CIR/P (univariate: HR, 0.62; 95% CI, 0.40 to 0.97; P = .027; multivariate: HR, 0.63; 95% CI, 0.41 to 0.98; P = .042) but no effect on nonrelapse mortality. Serial quantification of 25 mutations showed engraftment of 24 of 25 clones and disproportionate expansion in half of them. Donor-cell leukemia was observed in two recipients. OS was not affected by donor CHIP status (HR, 0.88; 95% CI, 0.65 to 1.321; P = .434). CONCLUSION: Allogeneic HSCT from donors with CHIP seems safe and results in similar survival in the setting of older, related donors. Future studies in younger and unrelated donors are warranted to extend these results. Confirmatory studies and mechanistic experiments are warranted to challenge the hypothesis that donor CHIP might foster cGVHD development and reduce relapse/progression risk.
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“One possible explanation for this finding is that the donor cells harboring the mutations were capable of mounting stronger immune responses against both normal host tissues and the tumor.”
From Clonal hematopoiesis in human aging and disease (2019) · cites this paper as [95]
In the citing paper
“Bone marrow transplant recipients with hematological malignancies who received donor marrow from carriers of CHIP had higher rates of graft-versus-host disease and reduced relapse rates 95.”
From Clonal hematopoiesis in human aging and disease (2019) · cites this paper as [95]
Citations
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Research works printed but not linked: 1
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Clonal hematopoiesis in human aging and disease
Jaiswal, S., & Ebert, B. L. (2019) · Science · doi:10.1126/science.aan4673 · Cited by 1,156
“Bonemarrow transplant recipients with hematological malignancies who received donor marrow from carriers of CHIP had higher rates of graft-versus-host disease and reduced relapse rates (96).”
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de Latour, R. P., Kulasekararaj, A. G., Iacobelli, S., Terwel, S. R., Cook, R., Griffin, M., Halkes, C. J. M., Récher, C., Barraco, F., Forcade, É., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2109965 · Cited by 312
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Donor Clonal Hematopoiesis and Recipient Outcomes After Transplantation
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Metadata
- Authors
- Frick, M., Chan, W., Arends, C. M., Hablesreiter, R., Halik, A., Heuser, M., Michonneau, D., Blau, O., Hoyer, K., Christen, F., Galan-Sousa, J., Noerenberg, D., Wais, V., Stadler, M., Yoshida, K., Schetelig, J., Schuler, E., Thol, F., Clappier, E., Christopeit, M., Ayuk, F., Bornhäuser, M., Blau, I. W., Ogawa, S., Zemojtel, T., Gerbitz, A., Wagner, E. M., Spriewald, B. M., Schrezenmeier, H., Kuchenbauer, F., Kobbe, G., Wiesneth, M., Koldehoff, M., Socié, G., Kroeger, N., Bullinger, L., Thiede, C., & Damm, F.
- Affiliations
- Humboldt-Universität zu Berlin (DE)
- Medizinische Hochschule Hannover (DE)
- Inserm (FR)
- University Hospital Ulm (DE)
- Kyoto University (JP)
- University Hospital Carl Gustav Carus (DE)
- Heinrich Heine University Düsseldorf (DE)
- Hôpital Saint-Louis (FR)
- Universität Hamburg (DE)
- Berlin Institute of Health (BIH) Core Genomics Facility, Charité, University Medical Center, Berlin, Germany
- Johannes Gutenberg University Mainz (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- German Red Cross (DE)
- Essen University Hospital (DE)
- David Michonneau and Gérard Socié, INSERM U1160, Institut Universitaire d’Hematologie, Paris/University Paris Diderot, Paris, France
- University Hospital Eppendorf, Hamburg, Germany
- German Cancer Research Center (DE)
- Charité - University Medical Center Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
- ORCID
- Frick, Mareike
- Arends, Christopher Maximilian
- Hablesreiter, Raphael
- Halik, Adriane
- Heuser, Michael
- Michonneau, David
- Blau, Olga
- Hoyer, Kaja
- Christen, Friederike
- Noerenberg, Daniel
- Yoshida, Kenichi
- Schetelig, Johannes
- Schuler, Esther
- Thol, Felicitas
- Clappier, Emmanuelle
- Christopeit, Maximilian
- Ayuk, Francis
- Bornhäuser, Martin
- Blau, Igor Wolfgang
- Ogawa, Seishi
- Gerbitz, Armin
- Wagner, Eva M.
- Schrezenmeier, Hubert
- Kuchenbauer, Florian
- Kobbe, Guido
- Koldehoff, Michael
- Bullinger, Lars
- Thiede, Christian
- Venue
- Journal of Clinical Oncology
- Published
- 2019-02-10
- Volume
- 37
- Issue
- 5
- Pages
- 375-385
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2899711966
- Cited by
- 223
- References
- 46
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 31 · 2023: 28 · 2022: 38 · 2021: 39 · 2020: 36 · 2019: 23
- FWCI
- 17.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (19H05656, 15H05909)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- clonal hematopoiesis of indeterminate potential, allogeneic hematopoietic stem cell transplantation, donor eligibility, chronic graft-versus-host disease, relapse and progression, clonal mutations, clonal expansion, donor cell leukemia, overall survival
- MeSH terms
- Age Factors, Aged, Female, Gene Frequency, Graft vs Host Disease, Hematopoiesis, Hematopoietic Stem Cells, Humans, Male, Middle Aged, Mutation, Retrospective Studies, Transplantation, Homologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Hematologic Neoplasms, Unrelated Donors
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